Chemically diverse activity-based probes with unexpected inhibitory mechanisms targeting trypsin-like serine proteases.

ABSTRACT: Activity-based probes (ABP) are molecules that bind covalently to the active form of an enzyme family, making them an attractive tool for target and biomarker identification and drug discovery. The present study describes the synthesis and biochemical characterization of novel activity-based probes targeting trypsin-like serine proteases. We developed an extensive library of activity-based probes with "clickable" affinity tags and a diaryl phosphonate warhead. A wide diversity was achieved by including natural amino acid analogs as well as basic polar residues as side chains. A detailed enzymatic characterization was performed in a panel of trypsin-like serine proteases. Their inhibitory potencies and kinetic profile were examined, and their IC₅₀ values, mechanism of inhibition,

SUBMITTER: Ramos-Llorca A 

PROVIDER: S-EPMC9849758 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature